Interferons are a family of proteins with a variety of biological activities including antiviral and anticellular activities. Although it is known that all actions of interferons are mediated by the products of interferon-inducible genes, the detailed mechanisms of actions of interferons have not been elucidated as yet. In this project, mechanisms of antiviral actions of interferons will be investigated. Specifically, how interferons inhibit the replication of vesicular stomatitis virus, of encephalomyocarditis virus and of retroviruses will be the subject of investigation. Which interferon-inducible gene product is responsible for which antiviral action and how and where in the viral life-cycle the interferon-mediated block is exerted are among the question to be asked. For these purpose, advantage will be taken of partially interferon-responsive cell clones isolated by us in which replication of one virus but not of another is inhibited by interferons. The role of a ribonuclease activity associated with subviral particles isolated from interferon-treated cells in inhibiting vesicular stomatitis viral primary transcription will be evaluated. Whether interferons can inhibit replication of encephalomyocarditis virus without using the ribonuclease L pathway will be investigated and at what step of retroviral DNA synthesis and integration the interferon-mediated block is will be determined.